The Insulin Resistance Syndrome: Impact on Lipoprotein Metabolism and Atherothrombosis

Abstract

Insulin resistance is a common metabolic abnormality that is associated with an increased risk of both atherosclerosis and type 2 diabetes. The phenotype of insulin resistance includes a dyslipidemia characterized by an elevation of very low-density lipoprotein triglyceride, a reduction in high-density lipoprotein cholesterol, and the presence of small, triglyceride-enriched low-density lipoproteins. The underlying metabolic abnormality driving this dylipidemia is an increased assembly and secretion of very low-density lipoprotein particles, leading to an increased plasma level of triglyceride. Hypertriglyceridemia, in turn, results in a reduction in the high-density lipoprotein level and the generation of small, dense low-density lipoproteins; these events are mediated by cholesteryl ester transfer protein. In addition, hypertension, obesity, and a prothrombotic state are also integral components of the insulin resistance syndrome. In this review, we will provide a pathophysiologic basis, based on studies on humans and in tissue culture, for the dyslipidemia of insulin resistance. We will also review the effects of insulin resistance on the coagulation and fibrinolytic pathways. It is hoped that this review will allow health professionals better to evaluate and treat their patients with insulin resistance, thereby reducing the very much increased risk of atherosclerotic cardiovascular disease carried by these individuals.

Multiple Abnormalities in Glucose and Energy Metabolism and Coordinated Changes in Levels of Adiponectin, Cytokines, and Adhesion Molecules in Subjects With Metabolic Syndrome

“…Impaired suppression of FFAs during hyperinsulinemia in subjects with the MetS contributes to elevated production of VLDL particles in the liver and thus hypertriglyceridemia. 23 However, causes of hypertriglyceridemia in the MetS are likely to be multifactorial, and other factors, in addition to the FFA flux into the liver, probably contribute to the dyslipidemia observed in these subjects.…”

The Metabolic Syndrome

“…22,23 However, HDL-C levels are often reduced in patients with insulin resistance even when fasting TG levels are normal. This suggests that other mechanisms contribute to the low HDL-C levels.…”

“…Dyslipidemia is a hallmark of the MetSyn and is characterized by elevated triglycerides (TG) and low levels of HDL-C. 22,23 Plasma LDL cholesterol (LDL-C) levels are often normal in patients with the MetSyn. A common finding, however, is that LDL particles are smaller and denser than normal, 22,23 a state believed to be associated with increased cardiovascular risk.…”

“…Conventional wisdom, based primarily on studies in cell culture, is that the increased flux of free fatty acids from the periphery to the liver in the insulin-resistant state drives hepatic TG synthesis, which in turn promotes the assembly and secretion of TG-containing VLDL. 23 Studies in animals and humans are needed in which the impact of hepatic TG synthesis on VLDL TG production is carefully assessed. It is likely that the causes of elevated TG levels in the MetSyn are multifactorial and not simply a function of increased free fatty acid flux to the liver.…”

Features of Dyslipoproteinemia in Type 2 Diabetes Mellitus Patients With Prior Myocardial Infarction

“…Як вiдомо, при iнсулiнорезистентно-стi [12] в жировiй клiтинi активується лiпо-лiз, що призводить до вивiльнення великої кiлькостi вiльних жирних кислот у кровотiк. Далi вiдбувається пiдвищення синтезу ТГ та ЛПДНЩ через доступнiсть їх основно-го субстрату, а також зниження деграда-цiї Апо В. Надлишкова продукцiя ЛПДНЩ з пiдвищеною секрецiєю ТГ та Апо В призво-дить до утворення дрiбних щiльних часток ЛПНЩ.…”